Acetic Acid → N-{4-[4-({(2S)-2-Hydroxy-3-[(2-oxo-2,3-dihydro-1H-benzimidazol-4-yl)oxy]propyl}-amino)-1-piperidineyl]phenyl}-5-(2-pyridinyl)-2-thiophenesulfonamide

HRID 1061378Notes

Reaction equation

HRID 1061378 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][S:15]([C:18]3[S:19][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:21][CH:22]=3)(=[O:17])=[O:16])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[OH:29][C@@H:30]([CH2:43][NH2:44])[CH2:31][O:32][C:33]1[C:41]2[NH:40][C:39](=[O:42])[NH:38][C:37]=2[CH:36]=[CH:35][CH:34]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>CN(C)C=O>[OH:29][C@H:30]([CH2:31][O:32][C:33]1[C:41]2[NH:40][C:39](=[O:42])[NH:38][C:37]=2[CH:36]=[CH:35][CH:34]=1)[CH2:43][NH:44][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]([NH:14][S:15]([C:18]3[S:19][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:21][CH:22]=3)(=[O:17])=[O:16])=[CH:12][CH:13]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 107991054-((2S)-3-Amino-2-hydroxy-propoxy)-1,3-dihydrobenzoimidazol-2-oneHCID 865845695-Pyridin-2-yl-thiophene-2-sulfonic acid [4-(4-oxo-piperidin-1-yl)-phenyl]-amide

Product 1

HCID 69654913N-{4-[4-({(2S)-2-Hydroxy-3-[(2-oxo-2,3-dihydro-1H-benzimidazol-4-yl)oxy]propyl}-amino)-1-piperidineyl]phenyl}-5-(2-pyridinyl)-2-thiophenesulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Pyridin-2-yl-thiophene-2-sulfonic acid [4-(4-oxo-piperidine-1-yl)-phenyl]-amide (which was obtained in Example 227) (0.21 g, 0.5 mmol) and (S)-4-[2-hydroxy-3-aminopropoxy]-1,3-dihydro-2H-benzimidazol-2-one (U.S. Pat. No. 5,786,356/1998) (0.11 g, 0.5 mmol) were mixed in dimethylformamide (10 mL) and then treated with sodium triacetoxyborohydride (0.16 g, 0.75 mmol) and acetic acid (0.045 g, 0.75 mmol). After stirring at room temperature under a nitrogen atmosphere for one day the mixture was quenched with 1N NaOH and then poured into a saturated aqueous NaHCO3. The precipitate which formed was collected and purified by preparative thin layer chromatography (16% MeOH/CH2CH2) to give the titled compound as a pale yellowish solid; 1H NMR (300 MHz, DMSO-d6) δ 1.25-1.40 (m, 2H), 1.80-1.90 (m, 2H), 2.50-2.90 (m, 5H), 3.53 (brd, J=9.0 Hz, 2H), 3.85-4.00 (m, 2H), 4.00-4.10 (m, 1H), 4.91 (brs, 1H), 6.56 (d, J=5.7 Hz, 1H), 6.61 (d, J=5.7 Hz, 1H), 6.80-6.90 (m, 3H), 6.96 (d, J=6.6Hz, 2H), 7.36 (dd, J=3.3, 1.2Hz, 1H), 7.41 (d, J=3.0Hz, 1H), 7.75 (d, J=3.0 Hz, 1H), 7.88 (dd, J=6.0, 1.2 Hz, 1H), 7.98 (d, J=6.0 Hz, 1H), 8.54 (d, J=3.3 Hz, 1H), 10.60 (s, 1H), 10.70 (s, 1H); MS (ES) m/z: 621.0 (MH+); HRMS Calcd. for C30H33N6O5S2 (MH+): 621.1954. Found: 621.1952.

Workup

  1. customwas quenched with 1N NaOH
  2. additionpoured into a saturated aqueous NaHCO3
  3. customThe precipitate which formed
  4. customwas collected
  5. custompurified by preparative thin layer chromatography (16% MeOH/CH2CH2)

Sources & evidence

ORD record
ord-1cf4c4c423114cbab5b0fda74d3da8a6
Source dataset
uspto-grants-2003_02
Patent number
US06525202B2

Reaction notes

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